We have recently developed a simple method for purifying two genetically determined forms of human serum cholinesterase, usual and atypical cholinesterase, in a high yield. This makes it possible to carry out the following studies: 1) to identify the amino acid alteration in atypical human serum cholinesterase, by peptide mapping followed by amino acid analysis, 2) to examine a wide variety of drugs (esters and amides) as substrates for purified serum cholinesterases, and to determine the relative effectiveness of atypical cholinesterase in hydrolyzing these drugs, and 3) to determine the degree of structural similarity between human serum cholinesterase (EC 3.1.1.8) and human red cell acetylcholinesterase (EC 3.1.1.7) by comparing the peptide maps of these two enzymes. This last experiment is a search for the physiologic function of serum cholinesterase, since it will test Koelle's hypothesis that butyrylcholinesterase (a classification that includes serum cholinesterase) is a precursor of acetylcholinesterase. These studies will give a more detailed understanding of how individual genetic variability affects drug metabolism.